rs6988000

Positions:

• chr8-134547291-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020863.4(ZFAT):​c.2977-14319G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,144 control chromosomes in the GnomAD database, including 3,841 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (3841 hom., cov: 33)
• Consequence: ZFAT NM_020863.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91

Genes affected

ZFAT (HGNC:19899): (zinc finger and AT-hook domain containing) This gene encodes a protein that likely binds DNA and functions as a transcriptional regulator involved in apoptosis and cell survival. This gene resides in a susceptibility locus for autoimmune thyroid disease (AITD) on chromosome 8q24. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Nov 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFAT	NM_020863.4	c.2977-14319G>A		intron_variant		ENST00000377838.8	NP_065914.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFAT	ENST00000377838.8	c.2977-14319G>A		intron_variant		1	NM_020863.4	ENSP00000367069	P4

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33389 AN: 152026 Hom.: 3836 Cov.: 33

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.194

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.220 AC: 33412 AN: 152144 Hom.: 3841 Cov.: 33 AF XY: 0.223 AC XY: 16601 AN XY: 74366

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.326

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.299

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.200

Alfa AF: 0.232 Hom.: 2190

Bravo AF: 0.210

Asia WGS AF: 0.344 AC: 1197 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.053
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6988000; hg19: chr8-135559534;